Download NONALLELIC GENE INTERACTIONS POLYGENIC INHERITANCE

NONALLELIC GENE INTERACTIONS
POLYGENIC INHERITANCE
1st year, 2nd semester, week 13
14. - 16.5.2007
© Aleš Panczak, ÚBLG 1. LF a VFN
Albinism – coat colour in the rat
P
genotype
phenotype
gametes
♀ SHR x ♂BN
ccBB
CCbb
albino
brown
cB
F1
Cb
(SHR x BN)
genotype
CcBb
phenotype
black
gametes
F2
Task 1/p. 95 KrOt
CB
Cb
cB
cb
(SHR x BN)
genotype
phenotype
2
Albinism – coat colour in the rat
3
Albinism – coat colour in the rat
4
Albinism – coat colour in the rat
BC
BC
BBCC
Bc
BBCc
black
Bc
BBCc
bc
BbCC
BbCC
black
BBcc
black
bC
bC
BbCc
black
BbCc
albino
bc
black
Bbcc
black
albino
BbCc
bbCC
bbCc
black
black
brown
brown
BbCc
Bbcc
bbCc
bbcc
black
albino
brown
albino
5
Albinism – coat colour in the rat
P
genotype
phenotype
gametes
SHR x BN
ccBB
CCbb
albino
brown
cB
F1
Cb
(SHR x BN)
genotype
CcBb
phenotype
black
gametes
F2
genotype
phenotype
Task 1/p. 95 KrOt
CB
Cb
cB
cb
(SHR x BN)
9 C-B- : 3 C-bb : 4 ccB-, ccbb
black brown albino
6
Bombay phenotype in the AB0 system
7
Task 3/p. 96 KrOt
Mother’s parents
gametes
HB
hB
H0
h0
H0
HHB0
gr. B
HhB0
gr. B
HH00
gr. 0
Hh00
gr. 0
h0
HhB0
gr. B
hhB0
gr. 0, anti-H
Hh00
gr. 0
hh00
gr. 0, anti-H
0
B
00
B?
A1
0
0
0
A1?
B0
0?
0?
A1B
A1B
gametes
of mother
hB
h0
Parents
of father
HA 1
HhA 1 B
gr. A1B
HhA 1 0
gr. A1
H0
HhB0
gr. B
Hh00
gr. 0
Bombay phenotype in the AB0 system
8
Bombay phenotype in the AB0 system
9
10
Bombay phenotype in the AB0 system
Bombay phenotype in the AB0 system
Supplementarity, recessive epistasis,
exemple of metabolic pathway.
11
H and AB0 loci as
recessive epistasis
Homozygocy for alleles of
one gene affects the
expression of a second gene.
• H gene (FUT1) is epistatic
to the AB0 gene.
• H substance is attached to
the cell surface.
• hh genotype = no H
substance (antigen).
• RBC of all AB0 genotypes
appear as type 0.
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Interaction of nonallelic genes
Phenotypic
ratios
F2
Bc1
Genotypes
A*** : aaaa
15 : 1
3:1
9:6:1
1:2:1
noncumulatives
with dominance
A*A* : A*aa + aaA* : aaaa
1:4:6:4:1
1:2:1
13
Duplicity genes
cumulatives
with dominance
cumulatives
without dominance
Regardless of order of active alleles
F2
AAAA AAAa
AAaa
Aaaa
aaaa
1
:
4
:
6
:
4
:
1
Bc
1
:
2
:
1
Segregation ratios
Pascal’s triangl
n
(1 + 1) n
1
1
2
1
3
1
4
1
5
1
6
1
7
8
14
1
1
7
8
3
5
6
4
20
8
1
5
15
35
70
4
1
10
35
56
1
6
15
2
3
10
21
28
1
2
4
Total
1
6
21
56
16
32
1
7
28
64
1
8
128
1
256
Polygenic inheritance – body height
Task 3/p. 93 KrOt
a) 200 cm
b) F 2 generation
No. of active
alleles
Body height
(cm)
Rate
c)
1
1
2
3
4
5
6
7
8
9
10
150 155 160 165 170 175 180 185 190 195 200
1
1:4:6:4:1
1:2:1
15
0
5 genes with additive effect without dominance
10
45
120 210 252 210 120
A 1a 1A 2a 2
x
10
1
A 1a 1A 2a 2
A 1A 1a 2a 2
x
A 1a 1A 2a 2
A 1A 1a 2a 2
x
x
A 1A 1a 2a 2
A 1A 1a 2a 2
45
a 1a 1A 2A 2
All of them
160 cm
= 2 active
alleles
Polygenic inheritance – body height
Task 3/p. 93 KrOt
No. of active alleles
Body height
Rate
0
1
2
3
4
5
6
7
8
9
10
150 155 160 165 170 175 180 185 190 195 200
1
10 45 120 210 252 210 120 45 10
1
250
200
frequency
150
100
50
0
150
155
160
165
170
175
180
185 190
Height (cm)
160 cm = 2 active alleles
possible genotypes: A1A1a2a2******, A1a1A2a2******, a1a1A2A2******
195
200
16
Recurrence risk estimates for diseases with
multifactorial etiology
1. Although
the disorder
is obviously
familial,
there
is no
reccur
.
risk
=
popul
.
incidence
&
I . dg . rel .
distinctive pattern of inheritance
within family
2. The recurrence risk to first-degree relatives is
approximately the square root of the population risk
(incidence) – Edwards’ formula
3. The risk is sharply lower for second-degree than for firstdegree relatives, but it declines less rapidly for more
remote relatives.
4. The risk is higher when more than one family member is
affected – for first-degree relatives, the value calculated
from Edwards’ formula is multiplied by 2, 3 etc.
5. The more severe the malformation, the greater the risk
6. If a multifactorial trait is more frequent in one sex than in
the other, the risk is higher for relatives of patients of the
less susceptible sex.
7. An increased risk when the parents are consanguineous
(multiple factors with additive effects may be involved)
8. Strongly affected by the environmental factors
17
Neural tube defect reccurence risk
Task 9/p. 94 KrOt
Congenital malformation with multifactorial ethiology and
polygenic inheritance, population frequency ca 0,0009
3%
3%
6%
>3%
18
Home work:
Task 1/p. 92 KrOt
Task 8/p. 94 KrOt
19